ObjectiveEndothelial nitric oxide exerts important effects on the regulation of vascular tone and structure. Variants of the endothelial nitric oxide synthase gene (eNOS) have been associated with hypertension and myocardial infarction, although some reports have shown negative linkage with hypertension. To examine whether the region encoding theeNOSgene is linked with physiological blood pressure variation, we undertook a linkage analysis of this region in the general population.DesignIn healthy volunteer families, we used two independent quantitative linkage analyses to examine the relationship between genotypes and phenotypes, with both parametric and non-parametric and single-locus and multi-point methods.MethodsWe selected 260 families comprising mother and father (aged 40–70 years) and two natural offspring (aged 18–30 years) from the Victorian Family Heart Study. After standardized measurement of clinical data and extraction of DNA, all family members were genotyped at five microsatellite loci including the CA repeat in theeNOSgene by a PCR method. The quantitative linkage analyses were conducted according to two different analysis programs, the Genetic Analysis System (GAS) and the MAPMAKER/SIBS.ResultsWith both linkage analyses, we found no linkage between any of the loci on chromosome 7q35–36 and the phenotypes systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, pulse rate, weight, height and body mass index.ConclusionBased on these results, we conclude that in this population theeNOSgene is not linked to the physiological variation of blood pressure and other related phenotypes.